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Sphingolipids are an important class of structural and signaling molecules within the cell. As sphingolipids have been implicated in the development and pathogenesis of insulin resistance and the metabolic syndrome, it is important to understand their regulation and metabolism. Although these lipids are initially produced through a common pathway, there is no “generic” sphingolipid. Indeed, the biophysical...
Heart disease is widely believed to develop from two pathological processes. Circulating lipoproteins containing the nondegradable lipid, cholesterol, accumulate within the arterial wall and perhaps are oxidized to more toxic lipids. Both lipid accumulation and vascular reaction to the lipids lead to the gradual thickening of the vascular wall. A second major process that in some circumstances is...
In recent years, the role of sphingolipids in physiology and pathophysiology of the heart attracted much attention. Ceramide was found to be involved in the pathogenesis of cardiac dysfunction in animal models of ischemia/reperfusion injury, Type 2 diabetes and lipotoxic cardiomyopathy. On the other hand, another member of this lipid family, namely sphingosine-1-phosphate, has been shown to possess...
Sphingolipids have emerged as key signaling molecules involved in the regulation of a variety of cellular functions including cell growth and differentiation, proliferation and apoptotic cell death. Sphingolipids in blood constitute part of the circulating lipoprotein particles (HDL, LDL and VLDL), carried by serum albumin and also present in blood cells and platelets. Recent lipidomic and proteomic...
Although obesity is a complex metabolic disorder often associated with insulin resistance, hyperinsulinemia and Type 2 diabetes, as well as with accelerated atherosclerosis, the molecular changes in obesity that promote these disorders are not completely understood. Several mechanisms have been proposed to explain how increased adipose tissue mass affects whole body insulin resistance and cardiovascular...
The development of a fatty liver predisposes individuals to an array of health problems including diabetes, cardiovascular disease and certain forms of cancer. Inhibition or genetic ablation of genes controlling sphingolipid synthesis in rodents resolves hepatic steatosis and in many cases wards off the health complications associated with excessive hepatic triglyceride accumulation. Examples include...
Glycosphingolipids are structural membrane components, residing largely in the plasma membrane with their sugar-moieties exposed at the cell’s surface. In recent times a crucial role for glycosphingolipids in insulin resistance has been proposed. A chronic state of insulin resistance is a rapidly increasing disease condition in Western and developing countries. It is considered to be the major underlying...
Glycosphingolipids, derived from the addition of sugar-moieties to the sphingolipid ceramide, are highly abundant in the kidney. Glycosphingolipids are known to play an important role in organ function at least in part from inherited lipid storage diseases such as Anderson-Fabry disease (Fabry’s disease; FD) that results from a mutation in alpha-galactosidase a (α-GLA or α-Gal A), the enzyme responsible...
This chapter focuses on the role of sphingolipids in the regulation of sterol-regulatory element binding protein (SREBP) dependent lipid synthesis and ATP-binding cassette protein ABCA1 and ABCG1 mediated lipid efflux, key regulators of cellular lipid homeostasis. Sphingolipid synthesis activates SREBPs independently of whether sphingolipid synthesis occurs through recycling or de novo pathways. SREBPs...
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